Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA0P7K)

• DTT Name: Complement factor B (CFB)
• Synonyms: Properdin factor B; PBF2; Glycinerich beta glycoprotein; Glycine-rich beta glycoprotein; GBG; Complement factor B Bb fragment; C3/C5 convertase; BFD; BF
• Gene Name: CFB
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Peptidase
• UniProt ID: CFAB_HUMAN
• TTD ID: T66011
• EC Number: EC 3.4.21.47
• Sequence:
  MGSNLSPQLCLMPFILGLLSGGVTTTPWSLARPQGSCSLEGVEIKGGSFRLLQEGQALEY
  VCPSGFYPYPVQTRTCRSTGSWSTLKTQDQKTVRKAECRAIHCPRPHDFENGEYWPRSPY
  YNVSDEISFHCYDGYTLRGSANRTCQVNGRWSGQTAICDNGAGYCSNPGIPIGTRKVGSQ
  YRLEDSVTYHCSRGLTLRGSQRRTCQEGGSWSGTEPSCQDSFMYDTPQEVAEAFLSSLTE
  TIEGVDAEDGHGPGEQQKRKIVLDPSGSMNIYLVLDGSDSIGASNFTGAKKCLVNLIEKV
  ASYGVKPRYGLVTYATYPKIWVKVSEADSSNADWVTKQLNEINYEDHKLKSGTNTKKALQ
  AVYSMMSWPDDVPPEGWNRTRHVIILMTDGLHNMGGDPITVIDEIRDLLYIGKDRKNPRE
  DYLDVYVFGVGPLVNQVNINALASKKDNEQHVFKVKDMENLEDVFYQMIDESQSLSLCGM
  VWEHRKGTDYHKQPWQAKISVIRPSKGHESCMGAVVSEYFVLTAAHCFTVDDKEHSIKVS
  VGGEKRDLEIEVVLFHPNYNINGKKEAGIPEFYDYDVALIKLKNKLKYGQTIRPICLPCT
  EGTTRALRLPPTTTCQQQKEELLPAQDIKALFVSEEEKKLTRKEVYIKNGDKKGSCERDA
  QYAPGYDKVKDISEVVTPRFLCTGGVSPYADPNTCRGDSGGPLIVHKRSRFIQVGVISWG
  VVDVCKNQKRQKQVPAHARDFHINLFQVLPWLKEKLQDEDLGFL
• Function: Factor B which is part of the alternate pathway of the complement system is cleaved by factor D into 2 fragments: Ba and Bb. Bb, a serine protease, then combines with complement factor 3b to generate the C3 or C5 convertase. It has also been implicated in proliferation and differentiation of preactivated B-lymphocytes, rapid spreading of peripheral blood monocytes, stimulation of lymphocyte blastogenesis and lysis of erythrocytes. Ba inhibits the proliferation of preactivated B-lymphocytes.
• KEGG Pathway:
  Complement and coagulation cascades (hsa04610)
  Staphylococcus aureus infection (hsa05150)
• Reactome Pathway:
  Activation of C3 and C5 (R-HSA-174577)
  Regulation of Complement cascade (R-HSA-977606)
  Alternative complement activation (R-HSA-173736)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Iptacopan	DM9EZM0	Paroxysmal nocturnal haemoglobinuria	3A21.0	Approved	[2]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LPN023	DM7BN5W	IgA nephropathy	MF8Y	Phase 2	[3]
RG6299	DMVJL8W	Geographic atrophy	9B75	Phase 2	[4]
SAR443809	DMSUQTW	Discovery agent	N.A.	Phase 1	[5]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CAB-2	DMQ4HUA	Coronary artery disease	BA80	Discontinued in Phase 1	[1]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
NM-9308	DMC89HI	Age-related macular degeneration	9B75.0	Investigative	[6]
PMID19743866C51	DMTX0ZJ	Discovery agent	N.A.	Investigative	[7]
TA-106	DME2PFQ	Asthma	CA23	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	1.70E-01	-0.12	-1.25
Asthma	CA23	Nasal and bronchial airway	1.63E-02	0.07	0.13

References

• [1] A soluble chimeric inhibitor of C3 and C5 convertases, complement activation blocker-2, prolongs graft survival in pig-to-rhesus monkey heart transplantation. Xenotransplantation. 2002 Mar;9(2):125-34.
• [2] Discovery of 4-((2 S,4 S)-4-Ethoxy-1-((5-methoxy-7-methyl-1 H-indol-4-yl)methyl)piperidin-2-yl)benzoic Acid (LNP023), a Factor B Inhibitor Specifically Designed To Be Applicable to Treating a Diverse Array of Complement Mediated Diseases. J Med Chem. 2020 Jun 11;63(11):5697-5722.
• [3] Complement Inhibitors in Clinical Trials for Glomerular Diseases. Front Immunol. 2019 Sep 27;10:2166.
• [4] Clinical pipeline report, company report or official report of Roche
• [5] Clinical pipeline report, company report or official report of Sanofi
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2339).
• [7] Structure-activity relationships for substrate-based inhibitors of human complement factor B. J Med Chem. 2009 Oct 8;52(19):6042-52.